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Reducing the risk of denosumab-induced hypocalcemia in patients with advanced chronic kidney disease: a quality improvement initiative

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Abstract

Summary

Denosumab can improve bone health in advanced kidney disease (CKD) but is associated with hypocalcemia. We created a clinical care pathway focused on the safe provision of denosumab in advanced CKD that reduced the risk of hypocalcemia by 37% at our hospital. Similar pathways could be adopted and tested in other centers.

Purpose

There is an increased risk of hypocalcemia with denosumab in advanced chronic kidney disease (CKD). We aimed to reduce the proportion of patients with advanced CKD who experienced denosumab-induced hypocalcemia at our center.

Methods

We conducted a quality improvement (QI) project of patients with CKD stage 3b or less (i.e., estimated glomerular filtration rate <45 mL/min/1.73m2 including dialysis) who were part of the Osteoporosis and Bone Disease Program at St. Joseph’s Health Care London (Canada) between December 2020 and January 2023. Our intervention was a clinical care pathway which optimized CKD mineral and bone disorder (CKD-MBD) and 25-hydroxyvitamin levels; provided calcium and vitamin D prophylaxis; promoted multidisciplinary communication between bone and kidney specialists; and carefully monitored calcium post-denosumab injection. Our primary outcome measure was the proportion of patients with hypocalcemia (defined by albumin-corrected serum calcium <1.9mmol/L) at 60 days. Process measures included the appropriate provision of calcium and vitamin D prophylaxis. Balance measures included the development of hypercalcemia and hyperphosphatemia following prophylaxis. We used plan-do-see-act cycles to study four tests of change and presented results using descriptive statistics and run charts.

Results

There were 6 patients with advanced CKD treated with denosumab prior to the implementation of our care pathway (March 2015–October 2020; 83% receiving dialysis). At the time of their denosumab injection, 83% were using 500–1000 mg of calcium, and 83% used 1000–2000 IU of vitamin D3. Fifty percent developed denosumab-induced hypocalcemia. Following the implementation of our care pathway, 15 patients (40% receiving dialysis) were treated with denosumab. Ninety-three percent received calcium at a daily dose of 350 to 2250 mg and 87% received 1000–2000 IU of vitamin D3. Thirteen percent developed denosumab-induced hypocalcemia. There was no hypercalcemia or hyperphosphatemia.

Conclusions

A clinical care pathway focused on the safe provision of denosumab in advanced CKD reduced the risk of hypocalcemia in patients treated in our hospital. Similar pathways could be adopted and tested in other centers.

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Author information

Authors and Affiliations

  1. Schulich School of Medicine and Dentistry, Western University, London, ON, Canada

    Tharsan Kanagalingam, Tayyab Khan, Nabil Sultan, Andrea Cowan, Jenny Thain & Kristin K Clemens

  2. Division of Endocrinology and Metabolism, Western University, London, ON, Canada

    Tayyab Khan & Kristin K Clemens

  3. St Joseph’s Health Care London, London, ON, Canada

    Tayyab Khan, Jenny Thain, Cindy Hoy & Kristin K Clemens

  4. Centre for Diabetes, Endocrinology, and Metabolism, St. Joseph’s Hospital, PO BOX 5777, STN B, London, Ontario, N6A 4V2, Canada

    Tayyab Khan & Kristin K Clemens

  5. London Health Sciences Centre, London, ON, Canada

    Nabil Sultan, Andrea Cowan & Seadna Ledger

  6. Division of Nephrology, Western University, London, ON, Canada

    Nabil Sultan & Andrea Cowan

  7. Division of Geriatrics, Western University, London, ON, Canada

    Jenny Thain

  8. Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

    Kristin K Clemens

  9. Lawson Health Research Institute, London, ON, Canada

    Kristin K Clemens

  10. ICES, London, ON, Canada

    Kristin K Clemens

Authors
  1. Tharsan Kanagalingam
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  2. Tayyab Khan
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  3. Nabil Sultan
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  4. Andrea Cowan
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  5. Jenny Thain
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  6. Cindy Hoy
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  7. Seadna Ledger
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  8. Kristin K Clemens
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Contributions

T. K. helped to conceptualize the project, collected and analyzed data, and drafted the manuscript. T. Khan conceptualized the protocol, interpreted the results, and reviewed the manuscript. N. S. conceptualized the protocol and tests of change, interpreted results, and reviewed the manuscript. J. T. conceptualized the protocol, interpreted the results, and reviewed the manuscript. C. H. and S. L. helped to develop and implement the protocol and reviewed the manuscript. K. C. conceptualized the project, analyzed data, interpreted results, and critically reviewed the manuscript.

Corresponding author

Correspondence to Kristin K Clemens.

Ethics declarations

Ethics approval

This project was classified as a QI investigation based on the requirements listed in the Tri-Council Policy Statement. Ethics approval was waived by our local research ethics board. All patients had confidential information protected.

Competing interests

T. Khan has received honoraria for speaking engagements from Amgen and has participated in Amgen advisory boards. T. Kanagalingam, N. Sultan, A. Cowan, J. Thain, C. Hoy, S. Ledger, and K. Clemens declare that they have no conflicts of interest.

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What is already known on this topic?

• Patients with chronic kidney disease (CKD) are at a heightened risk of fragility fracture. Fracture prevention can be complex due to the presence of CKD mineral and bone disorder (CKD-MBD) and altered drug metabolism.

• Denosumab can be prescribed to those with CKD but has been associated with an increased risk of hypocalcemia.

What this study adds

• We created a clinical care pathway to reduce denosumab-induced hypocalcemia in people with advanced CKD at our center (stage 3b CKD or less including those receiving dialysis). Components of the care pathway included optimization of CKD-MBD and 25-hydroxyvitamin D, calcium and vitamin D prophylaxis, an electronic order set, multidisciplinary communication, and close monitoring.

• Implementation of our pathway reduced the risk of denosumab-induced hypocalcemia by 37% over 1 year.

How might this study affect research, practice, or policy?

Our pathway can be modified and tested in other centers that prescribe denosumab to people with advanced CKD.

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Cite this article

Kanagalingam, T., Khan, T., Sultan, N. et al. Reducing the risk of denosumab-induced hypocalcemia in patients with advanced chronic kidney disease: a quality improvement initiative. Arch Osteoporos 18, 138 (2023). https://doi.org/10.1007/s11657-023-01341-8

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  • DOI: https://doi.org/10.1007/s11657-023-01341-8

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